Dataset Information

Model-Based Prediction of Acid Suppression and Proposal of a New Dosing Regimen of Fexuprazan in Humans.

ABSTRACT: Fexuprazan is a potassium-competitive acid blocker (P-CAB). The compounds in this newly developed drug family suppress intragastric acidity. As there are already other acid-suppressing drugs on the market, such as H₂ antagonists and proton pump inhibitors (PPIs), it would be informative to compare the biological effects of fexuprazan against another approved drug with the same indication. The drug concentration predicted by the pharmacokinetic (PK) model could serve as an input function for a pharmacodynamic (PD) model. The apparent pharmacokinetics of fexuprazan could be described by a simpler model. However, a physiologically based pharmacokinetic (PBPK) model was developed in a previous study. A one-compartment model was also proposed in the present study. Both the newly suggested model and the previously validated PBPK model were used as input functions of the PD models. Our simulation revealed that the effects of fexuprazan could be effectively simulated by the proposed PK-PD models. A PK-PD model was also proposed for the oral administration of the PPI reference drug esomeprazole. A model-based analysis was then performed for intragastric pH using several dosing methods. The expected pH could be predicted for both drugs under several dosing regimens using the proposed PK-PD models.

SUBMITTER: Kim MS

PROVIDER: S-EPMC9230547 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Model-Based Prediction of Acid Suppression and Proposal of a New Dosing Regimen of Fexuprazan in Humans.

Kim Min-Soo MS Lee Nora N Lee Areum A Chae Yoon-Jee YJ Chung Suk-Jae SJ Lee Kyeong-Ryoon KR

Pharmaceuticals (Basel, Switzerland) 20220603 6

Fexuprazan is a potassium-competitive acid blocker (P-CAB). The compounds in this newly developed drug family suppress intragastric acidity. As there are already other acid-suppressing drugs on the market, such as H<sub>2</sub> antagonists and proton pump inhibitors (PPIs), it would be informative to compare the biological effects of fexuprazan against another approved drug with the same indication. The drug concentration predicted by the pharmacokinetic (PK) model could serve as an input functi ...[more]

PMID: 35745628

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Project description:BackgroundThe antibody-drug conjugate sacituzumab govitecan is approved for metastatic triple-negative breast cancer and has shown promising results in various other types of cancer. Its costs may limit patient access to this novel effective treatment modality.ObjectiveThe purpose of this study was to develop an evidence-based rational dosing regimen that results in targeted drug exposure within the therapeutic range while minimizing financial toxicity, to improve treatment access.Patients and methodsExposure equivalent dosing strategies were developed based on pharmacokinetic modeling and simulation by using the published pharmacokinetic model developed by the license holder. The alternative dose was based on the principle of using complete vials to prevent spillage and on the established non-linear relationship between body weight and systemic exposure. Equivalent exposure compared to the approved dosing regimen of 10 mg/kg was aimed for. Equivalent exposure was conservatively defined as calculated geometric mean ratios within the 0.9-1.11 boundaries for area under the concentration-time curve (AUC), trough concentration (Ctrough) and maximum concentration (Cmax) of the alternative dosing regimen compared to the approved dosing regimen. Since different vial sizes are available for the European Union (EU) and United States (US) market, because body weight distributions differ between these populations, we performed our analysis for both scenarios.ResultsDosing regimens of sacituzumab govitecan for the EU (< 50 kg: 400 mg, 50-80 kg: 600 mg, and > 80 kg: 800 mg) and US population (< 40 kg: 360 mg, 40-65 kg: 540 mg, 65-90 kg: 720 mg, and > 90 kg: 900 mg) were developed, based on weight bands. The geometric mean ratios for all pharmacokinetic outcomes were within the predefined equivalence boundaries, while the quantity of drug used was 21.5% and 19.0% lower for the EU and US scenarios, respectively.ConclusionsWith the alternative dosing proposal, an approximately 20% reduction in drug expenses for sacituzumab govitecan can be realized while maintaining an equivalent and more evenly distributed exposure throughout the body weight range, without notable increases in pharmacokinetic variability.

Dataset Information

Model-Based Prediction of Acid Suppression and Proposal of a New Dosing Regimen of Fexuprazan in Humans.

Publications

Model-Based Prediction of Acid Suppression and Proposal of a New Dosing Regimen of Fexuprazan in Humans.

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